Fludeoxyglucose F 18-PET/CT Imaging in Assessing Response to Chemotherapy in Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin Lymphoma

Sponsor

University College, London (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00678327

Collaborator

Cancer Research UK (Other), Cancer Research UK & UCL Cancer Trials Centre (Other)

1,202

Enrollment

Location

Arms

160.1

Anticipated Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Imaging procedures, such as fludeoxyglucose F 18 (FDG)-PET/CT scan, done before, during, and after chemotherapy may help doctors assess a patient's response to treatment and help plan the best treatment. It is not yet known whether FDG-PET/CT imaging is effective in assessing response to chemotherapy in patients with newly diagnosed Hodgkin lymphoma.

PURPOSE: This randomized phase III trial is studying FDG-PET/CT imaging to see how well it works in assessing response to chemotherapy in patients with newly diagnosed stage II, stage III, or stage IV Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate Biological: filgrastim Biological: pegfilgrastim Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisolone Drug: procarbazine hydrochloride Drug: vinblastine sulfate Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

To determine if fludeoxyglucose F 18 (FDG)-PET/CT imaging can be reproducibly and effectively applied in the early assessment of response to chemotherapy in patients with newly diagnosed stage II-IV Hodgkin lymphoma.
To determine if a negative FDG-PET/CT scan after 2 courses of ABVD chemotherapy comprising doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine can be used to predict a group of patients for whom it is safe to reduce therapy by the subsequent omission of bleomycin, without detriment to progression-free survival.
To determine if treatment intensification in response to positive FDG-PET/CT imaging after 2 courses of ABVD chemotherapy can improve the outcome by comparison with previous series.

OUTLINE: This is a multicenter study.

Patients undergo fludeoxyglucose F 18 (FDG)-PET/CT imaging at baseline. Patients then receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response. Subsequent therapy is based on FDG-PET/CT scan results.

Negative FDG-PET/CT scan: Patients with a negative FDG-PET/CT scan are randomized to 1 of 2 treatment arms.
Arm I (ABVD chemotherapy): Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II (AVD chemotherapy): Patients receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Positive FDG-PET/CT scan: Patients with a positive FDG-PET/CT scan are assigned to 1 of 2 chemotherapy regimens, as determined by the participating center.
BEACOPP-14 chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride and oral prednisolone on days 1-7; and bleomycin IV and vincristine IV on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 8-13 OR pegfilgrastim SC once on day 8. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
BEACOPP-escalated chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride on days 1-7; oral prednisolone on days 1-14; and bleomycin IV and vincristine IV on day 8. Patients also receive G-CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of BEACOPP chemotherapy, patients undergo a third FDG-PET/CT scan to assess response. Patients with a negative FDG-PET/CT scan receive 2 more courses of BEACOPP-14 or 1 more course of BEACOPP-escalated chemotherapy. Patients with a persistently positive FDG-PET/CT scan may receive radiotherapy to sites of FDG uptake or salvage chemotherapy, at the investigator's discretion.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Study Design

Study Type:

Interventional

Actual Enrollment :

1202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Trial to Assess Response Adapted Therapy Using FDG-PET Imaging in Patients With Newly Diagnosed, Advanced Hodgkin Lymphoma

Actual Study Start Date :

Aug 29, 2008

Actual Primary Completion Date :

Jan 31, 2016

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Biological: bleomycin sulfate Given IV Drug: dacarbazine Given IV Drug: doxorubicin hydrochloride Given IV Drug: vinblastine sulfate Given IV
Active Comparator: Arm II Patients receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: dacarbazine Given IV Drug: doxorubicin hydrochloride Given IV Drug: vinblastine sulfate Given IV
Experimental: BEACOPP-14 chemotherapy Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride and oral prednisolone on days 1-7; and bleomycin IV and vincristine IV on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 8-13 OR pegfilgrastim SC once on day 8. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Biological: bleomycin sulfate Given IV Biological: filgrastim Given subcutaneously Biological: pegfilgrastim Given subcutaneously Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: prednisolone Given orally Drug: procarbazine hydrochloride Given orally Drug: vincristine sulfate Given IV
Experimental: BEACOPP-escalated chemotherapy Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride on days 1-7; oral prednisolone on days 1-14; and bleomycin IV and vincristine IV on day 8. Patients also receive G-CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Biological: bleomycin sulfate Given IV Biological: filgrastim Given subcutaneously Biological: pegfilgrastim Given subcutaneously Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: prednisolone Given orally Drug: procarbazine hydrochloride Given orally Drug: vincristine sulfate Given IV

Outcome Measures

Primary Outcome Measures

3-year progression-free survival [3 years]

Secondary Outcome Measures

Overall survival [5 years after last patient recruited]
Acute and chronic toxicity as assessed by NCI CTCAE v3.0 [5 years after last patient recruited]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed classical Hodgkin lymphoma (HL) meeting the following criteria:
Meets current WHO classification criteria (i.e., nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte-depleted)
Clinical stage IIB, III, or IV disease OR clinical stage IIA disease with adverse features, including any of the following:
Bulk mediastinal disease, defined as maximal transverse diameter of mass > 0.33 of the internal thoracic diameter at D5/6 interspace on routine chest x-ray
Disease outside the mediastinum and lymph node or lymph node mass > 10 cm in diameter
More than two sites of disease
Other poor-risk features that require treatment with full course combination chemotherapy
Newly diagnosed disease
No CNS or meningeal involvement by lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-3
Life expectancy > 3 months
ANC > 1,500/mm^3 (unless there is bone marrow infiltration by lymphoma)
Platelet count > 100,000/mm^3 (unless there is bone marrow infiltration by lymphoma)
Creatinine < 150% of upper limit of normal (ULN)
Bilirubin < 2.0 times ULN (unless attributed to lymphoma)
Transaminases < 2.5 times ULN (unless attributed to lymphoma)
LVEF ≥ 50% (in patients with a significant history of ischemic heart disease or hypertension)
Diffusion capacity within 25% of normal predicted value by lung function testing
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Amenable to the administration of a full course of chemotherapy, according to the investigator
Must have access to PET/CT scanning
No poorly controlled diabetes mellitus
No cardiac contraindication to doxorubicin hydrochloride, including abnormal contractility by ECHO or MUGA
No neurological contraindication to chemotherapy (e.g., pre-existing neuropathy)
No other concurrent uncontrolled medical condition
No other active malignant disease within the past 10 years, except fully excised basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
No known positivity for HIV, hepatitis B surface antigen, or hepatitis C
Routine testing, in the absence of risk factors, is not required
No medical or psychiatric condition that compromises the patient's ability to give informed consent